Comparison of the ability of basic and acidic fibroblast growth factor to stimulate the proliferation of an established keratinocyte cell line: modulation of their biological effects by heparin, transforming growth factor beta (TGF beta), and epidermal growth factor (EGF).
The bioactivity of both bFGF and aFGF in the BALB/MK-1 cell line has been compared to that of EGF. Our results indicate that, for that cell type, aFGF was far more potent than bFGF in inducing cell proliferation. In the presence of heparin, aFGF was as potent as EGF. In addition, excess bFGF has an inhibitory effect on the proliferation of MK cells exposed to a saturating concentration of aFGF, therefore acting as a partial agonist of aFGF. Surprisingly, bFGF, although it had low biological activity, was capable of synergizing the effect of EGF. In its presence, cultures exposed to saturating concentration of EGF have a final cell density 3- to 4-fold higher than that of counterpart cultures exposed to EGF alone. TGF beta, which in previous studies has been shown to inhibit the growth of keratinocytes, also inhibited the growth of BALB/MK-1 cells in response to either bFGF or aFGF. These studies suggest a role for FGF in regulating BALB/MK proliferation. aFGF provides positive growth signals which can be negatively modulated by excess bFGF or TGF beta, while bFGF, although a poor mitogen, could act by potentiating the effect of subsaturating concentrations of EGF.
Gospodarowicz
D
D
Cancer Research Institute, University of California San Francisco 94143.
Plouët
J
J
Malerstein
B
B
D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D015603:Keratinocytes / Q000166:cytology*; D011863:Radioimmunoassay; D013997:Time Factors; D015291:Transforming Growth Factors / Q000494:pharmacology*
D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D015291:Transforming Growth Factors; D006493:Heparin